T. Maudelonde et al., IN-VIVO STIMULATION BY TAMOXIFEN OF CATHEPSIN-D RNA LEVEL IN BREAST-CANCER, European journal of cancer, 30A(14), 1994, pp. 2049-2053
We have previously shown that 3 weeks of treatment with tamoxifen, of
patients with primary breast carcinomas, increased cytosolic cathepsin
D protein in oestrogen receptor (ER) positive tumours [Maudelonde et
al., Cancer 1989, 63, 1265-1270]. In order to investigate the mechanis
m of this increase and to eliminate a transient flare-up effect, we se
mi-quantified cathepsin D RNA levels by in situ hybridisation in 32 br
east carcinomas from patients treated with tamoxifen for 3 weeks prior
to surgery and in 35 breast cancer patients receiving no tamoxifen. W
e found that tamoxifen increased cathepsin D RNA level regardless of t
he ER status of the tumours. In ER positive tumours, tamoxifen increas
ed the cathepsin D RNA level to the same extent as cytosolic cathepsin
D protein but not in ER negative tumours. The induction of cathepsin
D RNA by tamoxifen in ER positive tumours was probably due to its agon
ist activity, also observed in vitro in breast cancer cell lines. Thes
e results suggest that the cathepsin D gene is inducible by oestrogens
in ER positive breast cancer as it is in breast cancer cell lines.